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PubMed2026

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans↗

PubMed2025

Antifungal treatment strategies and their impact on resistance development in clinical settings.

Invasive fungal diseases, particularly among immunocompromised patients, represent a growing clinical challenge due to limited therapeutic options, diagnostic delays and escalating antifungal resistance. Fungal pathogens employ diverse resistance mechanisms, including genetic mutations of antifungal target enzymes, biofilm formation, efflux pump overexpression and reduced drug penetration, which compromise the efficacy of clinically available antifungal classes. This review explores antifungal treatment modalities and evaluates approaches to mitigate resistance development. Advanced diagnostics and therapeutic drug monitoring are pivotal for enabling timely, targeted therapies and personalizing treatment plans, thus minimizing reliance on broad-spectrum agents. New antifungal agents, such as rezafungin, olorofim and fosmanogepix, along with long-acting and advanced formulations plus combination regimens, show substantial promise for managing resistance and improving treatment outcomes. Additionally, the development of immunotherapies and antifungal vaccines offers new avenues for bolstering host defences against fungal pathogens. Addressing antifungal resistance demands a multifaceted 'One Health' approach that integrates robust diagnostics, antifungal stewardship (AFS), precision medicine and collaborative global efforts. By advancing drug formulations, enhancing diagnostic tools and implementing forward-thinking AFS practices, the healthcare community can better tackle the escalating burden of fungal infections and deliver improved patient outcomes.

Antifungal Agents↗

PubMed2026

Management of complex lipid disorders in a community lipid clinic setting: Implementing a multidisciplinary model.

BACKGROUND: Large treatment gaps exist in the management of lipid disorders, and many high-risk patients have factors that complicate management efforts. While lipid clinics exist within academic medical centers, most of these patients are cared for in community settings. OBJECTIVE: To report our experience and results managing challenging and complex lipid disorders in a community-based lipid clinic. METHODS: We established a specialized lipid clinic in a community medical setting, with a focus on patients with management challenges and/or suspicion of a genetic lipid disorder, employing a multidisciplinary approach to optimize patient outcomes, emphasizing appropriate medical therapies and lipid genetic testing in selected patients. Retrospective electronic health record data were collected to analyze patient characteristics, treatment patterns, and lipid results. RESULTS: Over the period 2022 through 2024, 183 patients were seen (mean 63 years, 62% female). The challenging nature of the patient population was highlighted by high rates of statin intolerance (50%), no lipid medical therapy at baseline (50%), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], diabetes, and/or hypertension-61%). Despite this, over a mean follow-up of 9.4 ± 7.3 months, we observed a mean low-density lipoprotein cholesterol decrease of 49 mg/dL (-24.5%, P < .001), along with significant decreases in total cholesterol and triglycerides. Pathogenic dyslipidemia genetic variants were discovered in 21 patients (of 105 tested). Significant lipid improvements in the whole cohort, as well as multiple subgroups, were associated with greater utilization of combination therapies. CONCLUSION: Patients with complex lipid disorders can be successfully managed within a specialized lipid clinic in community medical settings. Applying such a multidisciplinary model outside of traditional academic medical centers offers the potential to raise the level of lipid management and ASCVD prevention more broadly in larger populations.

Combination medical therapy↗

PubMed2026

Polygenic risk score for early identification of coronary artery disease in a real-world clinical setting within the Latvian patient population.

STUDY OBJECTIVE: Polygenic risk scores (PRS) are increasingly recognized for their potential to improve coronary artery disease (CAD) prediction beyond traditional clinical models. This study evaluated the utility of genome-wide association study (GWAS) - derived PRS and pathway-specific PRS (PS-PRS) in the Latvian population, aiming to assess their association with CAD and compare their predictive performance with conventional risk factors. DESIGN PARTICIPANTS AND MAIN OUTCOME MEASURES: The study included 90 early-onset CAD patients and 43 controls with no evidence of atherosclerotic lesions on coronary angiography, with next-generation sequencing performed. PRS was calculated using 192 single nucleotide variants identified from the CARDIoGRAMplusC4D GWAS meta-analysis. The predictive accuracy of PRS, PS-PRS, clinical risk factors, and their combinations was analyzed via ROC curves. RESULTS: The average age was 48.7 years in CAD patients and 49.8 in controls. CAD patients showed significantly higher PRS (mean 0.31) compared to controls (mean - 0.65; p < 0.0001). PRS alone had moderate discriminatory power (AUC = 0.773), slightly lower than LDL cholesterol (AUC = 0.775) and total cholesterol (AUC = 0.821). Combining clinical risk factors improved prediction (AUC = 0.872), with the highest accuracy when PRS was integrated with all clinical factors (AUC = 0.933). The PRS distributions were significantly elevated in early-onset CAD patients across the angiogenesis/tissue repair pathway (p = 0.00038), inflammation pathway (p = 0.043), vascular remodelling pathway (p = 0.0116), and pathway of genes with unknown function in atherosclerosis (p = 0.0035), but overall PRS demonstrated superior discrimination compared to pathway-specific PRS. CONCLUSIONS: Incorporating PRS enhances early-onset CAD risk prediction. Pathway specific PRS had lower discriminative ability than the overall PRS.

Atherosclerosis↗

PubMed2026

Metagenomic sequencing in encephalitis diagnostics: Challenges and opportunities in clinical settings.

The primary aim of this study was to determine whether metagenomic next-generation sequencing (mNGS) can identify potential microbial agents responsible for encephalitis of unknown origin in immunocompetent patients, thereby enhancing clinical diagnostics. Cerebrospinal fluid samples from well-characterized patients (n = 17) diagnosed with encephalitis of unknown origin, according to Swedish national guidelines, were sequenced using mNGS using the Ion Torrent platform and analyzed using bioinformatic platforms. Samples from patients with known viral CNS infections i.e. HSV-2 meningitis (n = 4), VZV CNS infections (n = 3), enterovirus meningitis (n = 2), JCV CNS infection (n = 2) were used as controls for the methodology (n = 11). No viral agents were detected in 16/17 CSF samples from patients with encephalitis of unknown etiology. 13/17 CSF samples were analysed for the most common autoimmune antibodies and were negative. In one CSF sample from patients with encephalitis of unknown origin a Human pegivirus (HPgV) was detected. In 9/11 control CSF samples from patients with CNS infections, RNA or DNA of the known virus were detected. The main conclusion in this study was that the negative results were related to that the majority of included patients were immunocompetent. The finding of HPgV in a patient with unknown encephalitis was judged as a bystander. However, mNGS might detect more pathogens in other patient cohorts and this study implicates that a close collaboration between the clinical laboratory and the clinicians enables a safe implementation of metagenomics.

Humans↗

PubMed2025

Federated learning for the pathogenicity annotation of genetic variants in multi-site clinical settings.

MOTIVATION: Rare diseases collectively affect 5% of the population. However, fewer than 50% of rare disease patients receive a molecular diagnosis after whole genome sequencing. Supervised machine learning is a valuable approach for the pathogenicity scoring of human genetic variants. However, existing methods are often trained on curated but limited central repositories, resulting in poor accuracy when tested on external cohorts. Yet, large collections of variants generated at hospitals and research institutions remain inaccessible to machine-learning purposes because of privacy and legal constraints. Federated learning (FL) algorithms have been recently developed enabling institutions to collaboratively train models without sharing their local datasets. RESULTS: Here, we present a proof-of-concept study evaluating the effectiveness of FL for the clinical classification of genetic variants. A comprehensive array of diverse FL strategies was assessed for coding and non-coding Single Nucleotide Variants as well as Copy Number Variants. Our results showed that federated models generally achieved comparable or superior performance to traditional centralized learning. In addition, federated models reached a robust generalization to independent sets with smaller data fractions as compared to their centralized model counterparts. Our findings support the adoption of FL to establish secure multi-institutional collaborations in human variant interpretation. AVAILABILITY AND IMPLEMENTATION: All source code required to reproduce the results presented in this article, implemented in Python, is available under the GNU General Public License v3 at https://github.com/RausellLab/FedLearnVar.

Humans↗

PubMed2026

Impact of Commercial Artificial Intelligence on Radiologist Reading Time for Pulmonary Nodule Evaluation at Chest CT.

Background Chest CT is a primary method for identifying pulmonary nodules, yet interpreting scans remains time-intensive and demanding. Currently, artificial intelligence (AI) is expected to reduce reading times, but the effect of AI on reporting times in this setting is unknown. Purpose To evaluate the impact of a commercial AI software on radiologists' reading time for pulmonary nodule assessment on chest CT scans within a real-world clinical setting. Materials and Methods This retrospective study included patients who underwent chest CT examinations at a tertiary medical center between September 2021 and May 2024. The study period was divided into pre- and post-AI phases. The primary outcome was radiology reporting time. The association between AI implementation and reporting time was evaluated using a multivariable parametric Weibull shared frailty survival model adjusted for reader function, examination type, patient location, and requesting specialty, with clustering at the radiologist level. Interaction analyses assessed heterogeneity across prespecified subgroups. An exploratory extrapolation estimated projected workforce and financial impact. Results This study included 19 433 patients (mean age, 62 years ± 14.2 [SD]; 21 814 men; 39 323 chest CT examinations, 19 190 pre-AI, and 20 133 post-AI). AI implementation was associated with faster report completion (adjusted hazard ratio, 1.17; 95% CI: 1.14, 1.21; P < .001). The adjusted median reporting time decreased from 21.3 minutes pre-AI to 18.2 minutes post-AI (14.6% reduction; P < .001). Heterogeneity was observed across reader function (P < .001), examination type (P = .048), and requesting specialty (P = .03). The largest relative reductions were observed for CT thorax electrocardiogram-gated examinations (-41.1%; P < .001) and thoracic radiologists (-25.0%; P < .001), whereas emergency department examinations showed increased median reporting time (7.1%; P < .001). At institutional scan volumes (approximately 20 000-22 000 chest CT examinations annually), exploratory modeling suggested an approximate reduction of 0.5 full-time equivalent radiologist workload. Conclusion Implementation of commercial AI-assisted pulmonary nodule assessment on chest CT scans reduced radiologist reporting time in a real-world clinical setting. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.

Humans↗

PubMed2024

Development of a Fit-For-Purpose Multi-Marker Panel for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Humans↗

PubMed2024

Identification of a novel EYA4 likely pathogenic variant in a Chinese family with postlingual non-syndromic hearing loss and analysis of molecular epidemiology of EYA4 variants.

BACKGROUND: EYA4 variants are responsible for DFNA10 deafness. Due to its insidious onset and slow progression, hearing loss in autosomal dominant non-syndromic hearing loss (ADNSHL) is usually challenging to detect early in clinical settings, with limited intervention options. Genetic testing can aid in early detection of hearing loss, enabling timely intervention to reduce disability rates and improve the quality of life. METHODS: In this study, we report the case of a Chinese family with postlingual and progressive hearing loss that was passed down for four generations. Whole-exome sequencing (WES) was performed on DNA samples from the proband. Candidate variants identified in the proband and family members were confirmed via Sanger sequencing. In silico prediction tools and co-segregation analyses were used to assess the pathogenicity of identified variants. A literature review of known EYA4 variants was performed, analysing variant frequency, distribution characteristics across different populations, and genotype-phenotype correlations. RESULTS: We identified a novel EYA4 variant, c.1745_1748del (p.Glu582ValfsTer6), in a Chinese family with ADNSHL, and co-segregation with the family's phenotype was confirmed. The audiometry showed mid-to-high frequency downsloping hearing loss. To date, 52 pathogenic variants of EYA4 have been reported, with majority identified in Asian populations. Most observed are the missense and frameshift variants. CONCLUSIONS: A novel variant of EYA4 was identified in a Chinese family with postlingual hearing loss, contributing to the expanding spectrum of EYA4 variants. The audiological features of EYA4 variants are highly heterogeneous and often challenging to detect early in clinical settings. Our findings highlight the significance of genetic testing in patients presenting with postlingual hearing loss.

Humans↗

PubMed2025

Discovery of the Novel HLA Allele, HLA-B*13:01:24, in a Chinese Clinical Transplantation Setting.

HLA-B*13:01:24 differs from HLA-B*13:01:01:01 by one nucleotide substitution in codon 284 in exon 5.

Humans↗

PubMed2026

Ibuprofen versus acetaminophen for acute mild-to-moderate pain management in pediatric populations: a systematic review and meta-analysis of their efficacy.

UNLABELLED: Ibuprofen and acetaminophen are the most widely used analgesics in pediatric practice for the management of acute mild-to-moderate pain. Despite their widespread use, the comparative analgesic efficacy of these two agents in children remains a subject of ongoing debate, with existing evidence largely derived from heterogeneous clinical settings and small individual trials. Therefore, this study aimed to systematically review and meta-analyze randomized controlled trials comparing the analgesic efficacy of ibuprofen versus acetaminophen in pediatric populations with acute mild-to-moderate pain. A systematic literature search was conducted up to May 2026 in PubMed, Scopus, and Web of Science. The review was conducted and reported in accordance with the PRISMA-Children and Adolescents (PRISMA-C) 2026 reporting guideline. Eligible studies were randomized controlled trials comparing ibuprofen with acetaminophen in children and adolescents (defined as individuals aged 0 to < 18 years) with acute pain, reporting at least one extractable efficacy outcome. Continuous outcomes were synthesized as standardized mean differences (Hedges' g) using random-effects models; dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2 tool and certainty of evidence was evaluated using the GRADE framework. Eight randomized controlled trials enrolling 1325 participants were included. Three pediatric trials contributed to the primary continuous pain outcome meta-analysis (n = 196 analyzable participants), yielding a pooled SMD of - 0.28 (95% CI - 0.57 to 0.00; p = 0.052; I2 = 0%), indicating a small effect favoring ibuprofen that did not reach conventional statistical significance. Given the small number of contributing studies (k = 3), the I2 statistic should be interpreted with caution as it has limited power to detect heterogeneity in this context. For the dichotomous pain freedom outcome (2 trials, n = 114), no significant difference was observed (pooled RR 1.03, 95% CI 0.53-1.99; p = 0.93; I2 = 0%). A prespecified sensitivity analysis including an adult soft-tissue injury trial attenuated the pooled effect toward the null (SMD - 0.15, 95% CI - 0.38 to 0.09; p = 0.23; I2 = 36.6%). Narrative synthesis of additional studies generally demonstrated comparable analgesic efficacy between the two agents across postoperative and outpatient pediatric settings. The overall certainty of evidence was rated as low for both primary outcomes, primarily due to imprecision and indirectness. CONCLUSION: Current evidence from randomized controlled trials does not demonstrate a superiority of ibuprofen over acetaminophen for acute mild-to-moderate pain management in children. Both agents appear to provide clinically meaningful analgesia across heterogeneous pediatric pain settings. The clinical choice between agents should be guided by individual patient factors, including contraindications to NSAIDs, the inflammatory nature of the pain etiology, and patient-specific characteristics. The low certainty of evidence underscores the need for adequately powered, methodologically rigorous trials to definitively establish the comparative efficacy of these two analgesics in the pediatric population. WHAT IS KNOWN: • Ibuprofen and acetaminophen are the two most widely used non-opioid analgesics for acute mild-to-moderate pain in children, and both are recommended as first-line agents by major international guidelines. • Prior meta-analyses in mixed pediatric-adult populations have suggested a modest analgesic advantage of ibuprofen over acetaminophen, but pediatric-specific evidence has remained limited and methodologically heterogeneous. WHAT IS NEW: • This systematic review and meta-analysis, restricted to randomized controlled trials in pediatric populations, found that ibuprofen showed a small effect favoring pain reduction compared with acetaminophen (SMD - 0.28, p = 0.052), although this did not reach conventional statistical significance. • The analgesic advantage of ibuprofen may be more pronounced in pain etiologies with a significant inflammatory component (e.g., fractures). At the same time, both agents appear broadly equivalent in most other acute pediatric pain settings, supporting individualized analgesic selection based on clinical context and patient-specific factors.

Humans↗

PubMed2025

T cell subsets of urine-derived lymphocytes (UDLs) serve as an indicator of TILs and reflect immunological sex differences in bladder cancer.

BACKGROUND: Bladder cancer is unique among visceral malignancies in that urine, which can be easily obtained, has prolonged contact with bladder tumors. Urinary biomarkers offer the potential to provide insight into the host and tumor immune microenvironment to guide therapeutic strategies. We evaluated the immune cellular composition of urine (urine-derived lymphocytes (UDLs)) versus tumor (tumor-infiltrating lymphocytes (TILs)). METHODS: We employed high-dimensional flow cytometry analyses on immune cells from tumors (TILs), urine (UDLs), and peripheral blood (peripheral blood mononuclear cells) among patients with bladder cancer. We performed multiplexed immunofluorescence (mIF) of matched tumors to provide spatial context to our findings, comparing deep/invasive and superficial/urine-facing regions of matched tumors. RESULTS: Our findings suggest that the CD4+ and CD8+ T cell subsets of UDLs characterized by flow cytometry had similar phenotypic profiles to those found in TILs (cell clusters quantified by multidimensional scaling and differentiation states). Results of mIF imaging with a panel of phenotypic and functional T cell markers suggested that UDLs reflected TILs in both superficial and deep tumor sections. We also found sex-dependent patterns in TILs and UDLs, indicating the male bladder cancer tumor microenvironment is enriched in exhausted CD4+ and CD8+ T cells, while the female bladder cancer microenvironment is enriched for activated T cells. CONCLUSIONS: Assessment of UDLs opens avenues of non-invasive biomarker development in clinical settings where bladder cancer TILs are hypothesized to predict clinical response. UDLs may also reflect sex-based differences in antitumor immunity.

Humans↗

PubMed2026

Sodium Overload-Related Molecular Subtypes and a Four-Gene Prognostic Signature Predict Survival, Immune Landscape, and Therapeutic Response in Acute Myeloid Leukemia.

Sodium overload has recently emerged as a critical metabolic stressor involved in cancer progression; however, its molecular characteristics and clinical relevance in acute myeloid leukemia (AML) remain unexplored. RNA-seq data sets, clinical annotations, and mutational profiles of AML patients were annotations from The Cancer Genome Atlas and integrated with Genotype-Tissue Expression normal samples. Sodium overload-related genes (SORGs) were obtained from GeneCards. Differentially expressed SORGs (DESORGs) screened by applying the limma statistical model, followed by univariate Cox proportional hazards regression, consensus clustering, functional enrichment, immune infiltration analysis, and pathway evaluation. A prognostic signature was developed through least absolute shrinkage and selection operator regression followed by multivariate Cox modeling. The model's performance was further verified in two external GEO data sets (GSE71014 and GSE37642). Nomogram construction, subgroup analysis, tumor mutational burden (TMB) assessment, drug sensitivity prediction, transcription factor (TF) analysis, and competing endogenous RNA (ceRNA) network analyses were also performed. A total of 57 DESORGs were identified, and 2 sodium overload-related molecular subtypes exhibited distinct survival, immune infiltration, and inflammatory pathway activation. A robust four-gene signature (DOCK1, GABRE, HTR7, ACSM1) stratified patients into high- and low-risk categories with significantly different survival across training and validation cohorts. High-risk patients displayed increased immune infiltration, higher TMB, reduced sensitivity to multiple chemotherapeutic drugs, and inferior predicted response to PD-L1 blockade. TF and ceRNA networks revealed multilayered transcriptional and post-transcriptional regulation of the signature genes. This study identifies sodium overload-related molecular heterogeneity in AML and establishes a validated four-gene prognostic signature that integrates genomic, immunologic, and therapeutic features, offering potential utility for personalized risk assessment and treatment optimization.

Humans↗

PubMed2026

Occurrence of blaOXA-72 in a clinical isolate of carbapenem-resistant Acinetobacter pittii ST206 in Japan.

The development of carbapenem resistance in Acinetobacter spp., which are recognized as significant opportunistic pathogens, is of critical importance as it poses challenges to therapy and the control of healthcare-associated infections in clinical settings. This study investigated the genetic characteristics of a carbapenem-resistant A. pittii clinical isolate from a university hospital using whole-genome sequencing. The A. pittii strain SU8507, which was detected in the abdominal drainage fluid of a patient, exhibited resistance to imipenem (MIC: 128 μg/mL) and meropenem (MIC: 64 μg/mL) and produced positive results by the CIMTris method. A. pittii SU8507, belonging to ST206, harbored the blaOXA-72 and new variants of intrinsic blaOXA-213-like gene blaOXA-1222, which lacks an upstream insertion sequence element, and blaADC-1-like gene blaADC-343. The blaOXA-72 gene, flanked by XerC/XerD-like recombination sites, was located on a plasmid pSU8507, sized at 10,913 bp, carrying 13 predicted protein-coding genes. Complete pSU8507 containing mobA, repB, and the yoeB-yefM toxin-antitoxin genes, showed 98.9% nucleotide sequence identity and 75% coverage with plasmid pA2702 of the A. baylyi strain A2702, but a low BLAST MAX score. SU8507 harbored virulence genes involved in biofilm formation, types II and VI secretion systems, type IV pilus system, and serum resistance. This study describes the first isolation of an OXA-72-producing, carbapenem-resistant A. pittii clinical isolate in Japan. Given that the isolation rate of carbapenem-resistant Acinetobacter spp. Remains low in Japan, it is crucial to expand the scope of rapid, accurate carbapenemase detection to include not only A. baumannii, but also non-baumannii Acinetobacter spp.

Humans↗

PubMed2026

The Triad of NF-κB, HIF-1α, and Oxidative Stress in Hepatocellular Carcinoma: Pathogenesis, Clinical Challenges, and Therapeutic Potential of CIGB-552 in Liver Transplantation.

Hepatocellular carcinoma (HCC) represents a formidable oncological challenge characterized by complex molecular pathogenesis and limited therapeutic outcomes, particularly in the context of liver transplantation. As the sixth most commonly diagnosed cancer and the third leading cause of cancer-related mortality worldwide, HCC poses significant clinical challenges that demand innovative therapeutic approaches. Central to HCC development and progression is a pathogenic triad comprising nuclear factor-kappa B (NF-κB), hypoxia-inducible factor-1α (HIF-1α), and oxidative stress-three interconnected pathways that drive inflammation, angiogenesis, metabolic reprogramming, and cell survival. This comprehensive review examines the molecular mechanisms underlying this triad in HCC pathogenesis across different etiological contexts, including viral hepatitis and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). We critically analyse the unique clinical challenges posed by HCC in liver transplantation recipients, particularly the paradoxical requirement for immunosuppression alongside antitumor immunity, and constraints surrounding immunotherapy application. Furthermore, we present CIGB-552, a novel peptide therapeutic targeting COMMD1 (Copper Metabolism MURR1 Domain-containing protein 1), as a promising dual-function agent capable of simultaneously disrupting the pathogenic triad through NF-κB inhibition, HIF-1α suppression, and strategic modulation of oxidative stress via SOD1 regulation. The multimodal mechanism of CIGB-552 offers a theoretically rational therapeutic approach for HCC management in both pre-transplant and post-transplant settings. Clinical validation in the transplantation setting is required.

Humans↗

PubMed2023

MYH16 upregulation is associated with lung adenocarcinoma aggressiveness and immune infiltration.

Myosin heavy chain 16 (MYH16) may significantly affect cell cycle progression. Nevertheless, there is a lack of evidence about the clinical relevance of MYH16 upregulation in pan cancers, including lung adenocarcinoma (LUAD). MYH16 expression patterns were evaluated in various bioinformatics databases using The Cancer Genome Atlas data set. Clinical and pathological factor data were employed to risk-stratify patients. The Kaplan-Meier plotter approach was used to estimate survival rates. Tumor immune infiltration was explored via the TIMER tool, and gene set enrichment analysis (GSEA) was used to identify the pathways involved in MYH16 upregulation. The results showed that MYH16 was abnormally upregulated in pan cancers, including LUAD. MYH16 expression induction in LUAD was found to be related to the tumor stage. Furthermore, MYH16 upregulation was correlated with LUAD development and worse overall survival, particularly in women. Notably, MYH16 overexpression in LUAD tissues corresponded to the amount of immune infiltration in the tumor. Additionally, univariate Cox hazard regression analysis revealed that MYH16 may be an independent prognostic indicator for LUAD. Furthermore, a nomogram was constructed according to MYH16 expression and clinical characteristics. BMP6 expression deficiency may be a key factor contributing to MYH16 upregulation in LUAD. Finally, GSEA demonstrated that MYH16 might mediate meiosis and gene silencing through RNA signaling pathways. This study, for the first time, showed that MYH16 upregulation in LUAD is associated with various risk factors, increased cancer aggressiveness, enhanced infiltration of tumor immune cells, and reduced survival rates.

Female↗

PubMed2026

AgRP reflects glucocorticoid action: integrated experimental and clinical evidence.

PURPOSE: Glucocorticoids (GCs) are key regulators of energy homeostasis. Clinically, patients with Cushing's syndrome exhibit obesity, whereas adrenal insufficiency is associated with weight loss. However, circulating biomarkers reflecting GC action have not been established. Agouti-related protein (AgRP), an orexigenic neuropeptide, is upregulated by GC in the rodent hypothalamus. Here, we investigated whether AgRP is a surrogate marker of GC action through in vitro and in vivo experiments as well as a clinical study. METHODS: The GC-dependent transcriptional regulation of AgRP was examined using reporter assays in neuronal BE(2)C cells. In animal experiments, the effects of GC on hypothalamic AgRP mRNA expression in C57BL/6J mice were examined. Circulating AgRP levels were also analyzed in nine patients with adrenal Cushing's syndrome before and after surgery. RESULTS: Two functional glucocorticoid-responsive elements (GREs) were identified in the human AgRP gene promoter, through which GC enhanced AgRP transcriptional activity. In mice, corticosterone (CORT) administration induced hyperphagia and increased hypothalamic AgRP mRNA levels, which positively correlated with plasma CORT levels. In patients with adrenal Cushing's syndrome, circulating AgRP levels significantly decreased after surgery (118.7 ± 40.3 vs. 37.7 ± 9.5 pg/mL, p < 0.01) and positively correlated with serum cortisol levels (r = 0.79, p < 0.01). CONCLUSION: These findings demonstrate that GC positively regulates AgRP across molecular, animal, and clinical settings, supporting the hypothesis that circulating AgRP may serve as a surrogate indicator of GC action. Further studies are warranted to establish its clinical applicability.

Animals↗

PubMed2025

Multicenter Evaluation of a New Strip-Based Blood Glucose System for Point-of-Care Testing in Critical and Non-Critical Care Settings.

BACKGROUND: Evaluation of the performance of Cobas® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators. METHODS: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed by the Food and Drug Administration guidance criteria. RESULTS: Two studies are presented. In the first, 2678 samples (622 arterial, 706 capillary, 1203 venous, 147 heel stick) were collected from 1577 patients in 14 US and three European sites. All accuracy criteria were met for arterial and venous samples considering all data combined. BGMSA showed better accuracy than BGMSB for arterial, venous, and heel stick, and similar results to BGMSB for capillary WB vs venous comparator. No endogenous interference from pO2, hematocrit, and sodium was identified. BGMSA was also accurate when analyzing contrived samples used to show accuracy over a wide range of glucose concentrations, alone and when combined with extreme hematocrit. In the second study, 117 capillary fingerstick samples collected at one US site were measured on both BGMSA and the comparator, and all accuracy criteria were met. No clinically significant medical risks were observed via Diabetes Technology Society Error Grids. CONCLUSIONS: BGMSA was effective for determining blood glucose in venous, arterial, neonatal arterial, neonatal heel stick, and capillary WB samples.

Humans↗